1. Sepsis / Septic Shock for 3 rd year MBBS Dr. Ahmad Uzair Qureshi FCPS ( SURGERY) /MCPS ( SURGERY) MRCS ( ENGLAND) / Dip Med Edu (Cardiff) Colorectal Fellow Yonsei University, South Korea Assistant Professor of Surgery, King Edward Medical University, Lahore

4. SEPSIS “Is a systemic, harmful ( deleterious) host response to infection”.

5. SEPSIS “Is a systemic, deleterious host response to infection”. leading to

6. Severe Sepsis (acute organ dysfunction secondary to documented or suspected infection)

7. Severe Sepsis (acute organ dysfunction secondary to documented or suspected infection) leading to Dysfunction of organ(s) distant from the site of infection

8. SEPTIC SHOCK (severe sepsis plus hypoperfusion or hypotension not reversed with fluid resuscitation).”

9. INFECTION

10. Presence of microorganisms in a normally sterile site

11. INFECTION Presence of microorganisms in a normally sterile site Do Not confuse with “colonization,” which is the presence of microorganisms on an epithelial surface

12. Bacteremia

13. Cultivatable bacteria in the bloodstream May be transient and inconsequential;

14. Systemic inflammatory response syndrome (SIRS)

16. Early Host Responses to Infection Local Defenses: Walling Off and Killing Invading Microbes

17. Early Systemic Responses: Keeping Infection and Inflammation Localized

18. Acute-Phase Responses (Categorized According to Possible Roles in Defense) Anti-infective Increases synthesis of complement factors, microbe pattern-recognition molecules (mannose-binding lectin, LBP, CRP, CD14, others) Sequesters iron (lactoferrin, hepcidin) and zinc (metallothionein) Anti-inflammatory Releases anti-inflammatory neuroendocrine hormones (cortisol, ACTH, epinephrine, α- MSH) Increases synthesis of proteins that help prevent inflammation within the systemic compartment Cytokine antagonists (IL-1Ra, sTNF-Rs) Anti-inflammatory mediators (e.g., IL-4, IL-6, IL-6R, IL-10, IL-13, TGF-β) Protease inhibitors (e.g., α1-antiprotease) Antioxidants (haptoglobin) Reprograms circulating leukocytes (epinephrine, cortisol, PGE 2, ? other factors) Procoagulant Walls off infection, prevents systemic spread Increases synthesis or release of fibrinogen, PAI-1, C4b Decreases synthesis of protein C, antithrombin III Metabolic Preserves euglycemia, mobilizes fatty acids, amino acids Epinephrine, cortisol, glucagon, cytokines Thermoregulatory Inhibits microbial growth Fever Early Systemic Responses: Keeping Infection and Inflammation Localized

19. Harmful Responses to Infection: Severe Sepsis and Septic Shock Develop when normally adaptive stress responses are pushed beyond their ability to be protective. “Hypofunction” implies an inadequate level of activity, whereas “dysfunction” suggests that organ performance is in some way abnormal.

20. CONCEPTs 1.Microvascular derangement 2.Mitochondrial dysfunction. TWO Theories

21. An extension of the body's normal neuroendocrine responses to stress An exhaustion of ATP in critical organs when the inflammatory stimulus is too strong or too prolonged.

22. Cytokines circulate via the blood and induce injury to the vascular endothelium and/or microcirculation in different organs. An extension of the body's normal neuroendocrine responses to stress An exhaustion of ATP in critical organs when the inflammatory stimulus is too strong or too prolonged.

23. Septic Shock Opportunistic commensal bacteria typically invade across disrupted epithelia. Hosts in whom immunosuppressive acute-phase responses are already occurring because of illness, injury, or infection. Host is unable to kill the bacteria because of mechanical failure (obstructed drainage pathway), immunosuppression (neutropenia, “endogenous immunosuppression”)

24. These bacteria invade the bloodstream when local defenses are unable to kill or contain them; bacteremia. Locally-produced mediators act as trigger for severe sepsis and septic shock Outcome is strongly related to the patient's underlying physiologic fitness.

26. Pathogenic microbes/virus that can survive and multiply in previously healthy humans. the microbes/viruses may enter the bloodstream, infect vascular endothelial cells and/or blood cells, and release toxins. The circulating microbes may provoke both shock and profound coagulopathy that not uncommonly results in hemorrhage and/or arterial thrombosis

27. DIAGNOSTIC CRITERIA

31. Initial Resuscitation and Infection Issues A. Initial Resuscitation (Goals during the first 6 hrs of resuscitation) 1.Hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L a)Central venous pressure 8–12 mm Hg b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively

32. B. Diagnosis Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy Imaging studies performed promptly to confirm a potential source of infection (UG).

33. C. Antimicrobial Therapy Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens Antimicrobial regimen should be reassessed daily for potential deescalation. Use of low procalcitonin levels in the discontinuation of empiric antibiotics Combination empirical therapy for neutropenic respiratory failure and septic shock,

35. TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION*: 1. Measure lactate level 2. Obtain blood cultures prior to administration of antibiotics 3. Administer broad spectrum antibiotics 4. Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L

36. TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION: 5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg 6. In the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, re-assess volume status and tissue perfusion 7. Re- measure lactate if initial lactate elevated.

37. Fluid Therapy of Severe Sepsis Crystalloids as the initial fluid of choice Against the use of hydroxyethyl starches Albumin when substantial amounts of crystalloids (grade 2C). Initial fluid challenge a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). Fluid challenge technique be applied Change in pulse pressure, Stroke volume variation) Arterial pressure, Heart rate

38. Vasopressors Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg Norepinephrine as the first choice vasopressor. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents). Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg. patients with low risk of tachyarrhythmias and absolute or relative bradycardia).

39. Hemodynamic Support and Adjunctive Therapy Inotropic Therapy Corticosteroids Blood Product Administration. Immunoglobulins Mechanical Ventilation of Sepsis-Induced ARDS Sedation, Analgesia, and Neuromuscular Blockade in Sepsis Glucose Control Renal Replacement Therapy Bicarbonate Therapy Deep Vein ThrombosisProphylaxis Nutrition

40. For any queries +923144001410 or ahmeduzairq@gmail.com